Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q23.33 | {Obesity, susceptibility to} | 607514 | 3 | FFAR4 | 609044 |
A number sign (#) is used with this entry because mutation in the FFAR4 gene (609044) is associated with markedly increased risk of obesity.
For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641.
To evaluate potential epistatic interactions among 5 regions, on chromosomes 7q31, flanking leptin (164160), 10p (603188), 10q, 10cen, and 20q13 (602025), that had been linked to obesity phenotypes (see 601665), Dong et al. (2003) conducted pairwise correlation analyses based on alleles shared identical by descent (IBD) for independent obese affected sib pairs, and determined family-specific nonparametric linkage (NPL) scores in 244 families. The correlation analyses were also conducted separately, by race, through use of race-specific allele frequencies. Both the affected sib pair-specific IBD-sharing probability and the family-specific NPL score revealed that there were strong positive correlations between 10q (88-97 cM) and 20q (65-83 cM), through single-point and multipoint analyses with 3 obesity thresholds across African American and European American samples. The results from multiple methods and correlated phenotypes were considered consistent with epistatic interactions between loci on chromosomes 20 and 10 playing a role in extreme human obesity.
Ichimura et al. (2012) studied mice deficient in Ffar4, or Gpr120, and found that those fed a high-fat diet developed obesity, glucose intolerance, and fatty liver. They demonstrated in humans that GPR120 expression in adipose tissue was significantly higher in obese individuals than in lean individuals. Ichimura et al. (2012) then identified a missense mutation, R270H (609044.0001), that inhibits GPR120 signaling activity and was shown to increase the risk of obesity in multiple European populations (odds ratio 1.62; 95% confidence interval 1.31-2.00; P = 8.00 x 10(-6)).
Dong, C., Wang, S., Li, W.-D., Li, D., Zhao, H., Price, R. A. Interacting genetic loci on chromosomes 20 and 10 influence extreme human obesity. Am. J. Hum. Genet. 72: 115-124, 2003. [PubMed: 12478478] [Full Text: https://doi.org/10.1086/345648]
Ichimura, A., Hirasawa, A., Poulain-Godefroy, O., Bonnefond, A., Hara, T., Yengo, L., Kimura, I., Leloire, A., Liu, N., Iida, K., Choquet, H., Besnard, P., and 32 others. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483: 350-354, 2012. [PubMed: 22343897] [Full Text: https://doi.org/10.1038/nature10798]